Accounting for cross-immunity can improve forecast accuracy during influenza epidemics

Previous exposure to influenza viruses confers cross-immunity against future infections with related strains. However, this is not always accounted for explicitly in mathematical models used for forecasting during influenza outbreaks. We show that, if an influenza outbreak is due to a strain that is similar to one that has emerged previously, then accounting for cross-immunity explicitly can improve the accuracy of real-time forecasts. To do this, we consider two infectious disease outbreak forecasting models. In the first (the "1-group model"), all individuals are assumed to be identical and cross-immunity is not accounted for. In the second (the "2-group model"), individuals who have previously been infected by a related strain are assumed to be less likely to experience severe disease, and therefore recover more quickly, than immunologically naive individuals. We fit both models to estimated case notification data (including symptomatic individuals as well as laboratory-confirmed cases) from Japan from the 2009 H1N1 influenza pandemic, and then generate synthetic data for a future outbreak by assuming that the 2-group model represents the epidemiology of influenza infections more accurately. We use the 1-group model (as well as the 2-group model for comparison) to generate forecasts that would be obtained in real-time as the future outbreak is ongoing, using parameter values estimated from the 2009 epidemic as informative priors, motivated by the fact that without using prior information from 2009, the forecasts are highly uncertain. In the scenario that we consider, the 1-group model only produces accurate outbreak forecasts once the peak of the epidemic has passed, even when the values of important epidemiological parameters such as the lengths of the mean incubation and infectious periods are known exactly. As a result, it is necessary to use the more epidemiologically realistic 2-group model to generate accurate forecasts. Accounting for cross-immunity driven by exposures in previous outbreaks explicitly is expected to improve the accuracy of epidemiological modelling forecasts during influenza outbreaks.